Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies

Abstract

Traditional cancer treatment approaches have focused on surgery, radiation therapy, and cytotoxic chemotherapy. However, with rare exceptions, metastatic cancers were considered to be incurable by traditional therapy. Over the past 20 years a fourth modality -immunotherapy -has emerged as a potentially curative approach for patients with advanced metastatic cancer. However, in many patients cancer "finds a way" to evade the anti-tumor effects of immunotherapy. Immunotherapy resistance mechanisms can be employed by both cancer cells and the non-cancer elements of tumor microenvironment. This review focuses on the resistance mechanisms that are specifically mediated by cancer cells. In order to extend the impact of immunotherapy to more patients and across all cancer types, and to inhibit the development of acquired resistance, the underlying biology driving immune escape needs to be better understood. Elucidating mechanisms of immune escape may shed light on new therapeutic targets, and lead to successful combination therapeutic strategies.

Evaluating the Combination of Radioimmunotherapy and Immunotherapy in a Melanoma Mouse Model

“…Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers [1]. The combinations of immunotherapy with other treatment modalities are also being actively investigated [2]. One of the challenges to investigate such combinations is to identify suitable mouse models with intact immune systems for the pre-clinical experiments.…”

Advances in Nanotechnology Development to Overcome Current Roadblocks in CAR-T Therapy for Solid Tumors

“…To reset the suppressive solid tumor microenvironment, inhibitors targeting checkpoint molecules (such as CTLA-4, PD-1 and PD-L1) and CAR-T therapy were used in combination ( 70 , 71 ). The disadvantages of using immune-checkpoint inhibitors (ICIs) include the emergence of a series of new immune-related adverse events and systemic toxicities ( 72 ). Stephan et al.…”

Using nanoparticles forin situvaccination against cancer: mechanisms and immunotherapy benefits

“…CTLA-4 on Tregulatory cells can also interact with the B7s on APCs to inhibit its function in a tumor. Tumor cells can also reduce their antigen presentation by inducing mutation and loss of b-2-microglobulin (B2M), which processes tumor antigens, deleting MHC class I polypeptiderelated sequence A and B (MICA/B) that reduces detection by the NK cells, reducing the expression of Fas, TRAILs, Caspase 8 that activates the apoptotic pathways, secreting immunosuppressive metabolites (2,3-dioxygenase (IDO) that reduces T-cell proliferations, and altering the oncogenic signals that affect T-cell responses [156]. NP-ISVs have direct access to tumor and immune cell population, and thus can target such immunosuppressive signals in CBT refractory tumors.…”